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On schedule 3 at a TMZ dose of 75 mg/m/day on days 1–5 while receiving pegfilgrastim, all six patients were assessable for toxicity. H.), Duke University Medical Center, Durham, NC, USADepartments of Surgery (J. One patient experienced grade 3 neutropenia, which was not dose limiting. This study was supported by National Institute of Neurological Disorders and Stroke grant 5P50 NS20023-25, National Institutes of Health (NIH) Specialized Programs of Research Excellence grant 5P50 CA108786-4, and NIH merit award R37 CA 011898-38. Delayed repletion of O6-methylguanine-DNA methyltransferase resulting in failure to protect the human glioblastoma cell line SF767 from temozolomide-induced cytotoxicity. Phase I trial of polifeprosan 20 with carmustine implant plus continuous infusion of intravenous O6-benzylguanine in adults with recurrent malignant glioma: new approaches to brain tumor therapy CNS consortium trial. Other strategies to overcome TMZ resistance mediated by AGT include a dose-dense TMZ schedule, an approach currently being evaluated by the Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer. Hirose Y, Kreklau EL, Erickson LC, Berger MS, Pieper RO. If your browser does not accept cookies, you cannot view this site.There are many reasons why a cookie could not be set correctly.Use the Publish and About menus above, or search the PLOS websites. H.), Duke University Medical Center, Durham, NC, USADepartments of Surgery (J.
Demographic and clinical characteristics of patients are detailed in Table 2./day on days 2–5, six of seven patients were assessable for toxicity.
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Two patients developed grade 3 neutropenia, which was not dose limiting.
Two patients experienced a DLT: one patient developed grade 4 leukopenia with grade 4 thrombocytopenia, and another patient developed grade 4 neutropenia with grade 3 thrombocytopenia.
If two instances of DLT were observed at a dose level, the MTD was determined to be surpassed, and a total of six patients were treated at the previous level to ensure its tolerability.